Process of making hydroxylamine and mandelic acid



PdteritedFeb- 7, 1939 a I p t n .rif f STATES P E T OFFICE ard OilDevelopment Company, a corporation vof Delaware "No Drawing. ApplicationJuly 29, 1937,

'g- Serial No. 156,337

seam.- ((1260- 520) e ;;This invention haszfollts purpose the simul-,"the abovetuses hydroxylamine finds furtheruse taneous productionof'hydroxylamine'and alphai as an important photographic developer.

"hydro xy-carboxylic acids. .It-is particularly ap- I The process in useat the present time for the piicable to the preparationuof hydroxylamineand production of mandelic acidconsists in condensing 5,mandelic:acid. 1..I, V J bei'izaldehvde with hydrogen cyanide gas, oroi.

The present invention comprises the conden-" reacting thebenzaldehyde-sodium bisulphite consa'tion'of ,aldehydes (aliphatic;cycloparailinic, densation product with sodium cyanide, to producearomatic,'or'substituted) with a primary alimandelonitrile, CcHs-CHOH-CN, which in turn phatic nitro compound (nitromethane), to proishydrolyzed to mandelic acid. This method, 10 'duce' nitro-alcohols orsubstituted nitro-alco' however, possesses severalvery seriousdisadvanl0 hols, followed by subsequent hydrolysis of saidtages,-namely:'(1) The useof hydrogen cyanide nitro-alcohols, using acidhydrolytic agents, to (prussic acid) or metallic cyanides presents ahydroxylamine or its salts, and alpha-hydroxy- 1 very dangerous healthhazard, both from the carboxylic acids or substituted" alpha hydroxystandpointof carrying out the reaction and also carboxylic acids. l r .1p

"Furthermore, this invention relates to the use, cyanides to be usedmedicinally; (2) the cost as starting ;materials, of intermediates whichof preparing hydrogen cyanide is considerable in "may be derived frompetroleum hydrocarbons. comparison tonitromethanewhichmay be.man Theproducts obtained by the process of this ufactured from petroleumhydrocarbons at a of obtaining mandelic acid sufliciently free of 16invention are important and highly desirable very low cost; (3) theintermediate formed by 20 materials. Mandelic acid, for example, is usedthe condensation of benzaldehyde with hydrovery extensively in themedical profession for gencyanide, mandelonitriie, lsa very unstablecombating infections or the kidneys and of the compound and must beutilized as quickly as genito-urinary tract,- which in turn result fromformed in order to obtain suitable yieldsof final 2 the ravages of themicro-organisms Bacillus product. This mandelonitrile, CsH5 QI-IOH-CN,

colon which-normally inhabits the intestinal readily undergoes arearrangement to the isonitract. In view of the fact that the kidney andtrile, CcHs-CHOH-NC, which (as is well known) urinary tract are very"inaccessible for direct cannot be hydrolyzed to mandelic acid. Incontreatment it is necessary to attack these .aiitrast to this, thenitroalcohols formed as inter- 9 ments fby indirect courses. It has beenfound mediates in thereaction set forth by the present that mandelicacid and closely related materials invention, are quite stable and maybe kept with- I have the. ability, when ing'ested'orally, ofbein'g outappreciabledecomposition; (4) the hydroly- 'cariri'ed by body fluidstothe afi'ected regions, in sis of mandelonitrile must be carried out inthe which regionsthe mandelic compounds. causea, cold (consequentlynecessitating a long reaction 7 5 su'illcient lowering of'pH,,orincrease in acidity, timeiin order toobtaina productof suitable as soastdrnder the harmful Bacilliicoli germs. color. If this hydrolysis iscarried out at higher innocuous 'The acidity produced inthismantemperatures, the mandelic f acid obtained is, her issumcientto killinfectious organisms but highly colored, this c l r b in v ry p rsis entv not, strong-en ugh to cause tissue deterioration. d thereby offeringdifflculty in fi op a- 4() H x m'm h the other hand, is very tions.Even'when hydrolysis is carried out in the 40 iportanhboth in chemistryand in they medical cold, the product is deeply colored and must be IProfession. In the'forrner case it finds us allowed to stand in the airand light for at least a reducing agent in analytical work, for example,twenty'mur hours before the 'refimng operation inthe determination ofgold, silver and mercury, lsbegun offering an addvittonal Obstacle; (5)and the likeyas an intermediate inchemical f a e g' by.the bfinzalde'synthesis, for example, in the'preparatmn of dif 5 33 cyan gf 15 m 1y 9?methyl glyoitime which is an important .chemi- 8 W1 ammomlfm 0 wide fromwhlth v a r a I it is difficult to separate, (6) the mandelonitrilecalreagent, and for many .other purposes. In

g 4 reaction furnishes no valuable by product as is themedical professon it is of considerable thera-v the case in the present invention ywhich useful 50 valuefrqmihe.standpoint g em 3 5?- and desirablehydroxylamine is" produced; (7) a t l/63 7 llt s m d i (and is "alsomuch longer timefis required by the benzalde-, used inthe treatmentofcertain skin diseases, hyde-hydrogen cyanide reaction for producingsuch as chronic P D e p s, nd mandelic acid than is required by theprocess 01 other dermatological ailments. -,In addition to the presentinvention.- 55

The present invention provides a reaction which is easily manipulatedand which furnishes two highly desirable products, each of which may beeasily obtained in a high state of purity free from objectionable color.7

The initial materials utilized according to this invention may, ,asmentioned hereinbefore, be made'from petroleum hydrocarbons.Benzaldehyde, which is a common everyday chemical, can be made by anyofthe following, and various other, methods. For example, toluene may betreated in the vaporphase, and in thepresence,

of suitable catalysts, with air or other-oxygencontaining gas, such asnitrogen tetroxide, to produce benzaldehyde. Or, the oxidation oftoluene" may be carried out in the liquid phase using as the activeoxidizing agent such materials as chromic acid, permanganates, manganesedioxide, and the like. Benzaldehyde may also be prepared from toluene,by subjecting the latter material to chlorination in the presence ofsunlight and hydrolyzing the benzyl chloride thus ;formed.-.

Still other methods for producing this aldehyde consist'in reactingcarbon monoxide with benzene 5 in the presence of hydrogenchloride andalumi num chloride, or by reacting chromyl: chloride with ethyl benzene.v f

Nithromethane, on the other hand, whichis a stable, colorless,non-explosive liquid of pleasant 40 of nitrogen, for example, nitrogentetroxide. An-

- other method for producing this nitro compound consistsin treatingmethane gas with chlorine in'the presence of light and subsequentlyreacting dehydes suitable for ,my purpose comprise not the methylchloride with 'a metallic nitrite, as for example, silver nitrite, theproducts of the latter reaction being nitromethane, along with somemethyl nitrite, and silver chloride.

This invention possesses the further advantage,

that aldehydes in general may be employed, al

only those derived from aliphatic, aromatic,'or

cycloparaffinic hydrocarbons, but alsoalkyl, aryl,

or aralkyl derivatives of such aldehydes as well i as their 'nitrohalo,-, sulphonyl-, hydroxyl-, and I The 'substituent groups may bepresent either in the ring: or on other. substitution products.

the hydrocarbon chains and in the case of the aromatic andcycloparafiinic aldehydes, the aldo grouping may be either attacheddirectly to, or separated by one or more alkyl groups from, the

cyclic nucleus.

According. to the present invention the reaction 7 may be carried out bymixing the reactants (nitromethane and an aldehyde) at room temperatureor below in a suitablesolvent, or .if desired... at higher temperatures,using as catalyst an alkaline material, (e. g., potassiumhydroxide, so-

dium metal, caustic soda, and the like),'andallowing thereaction toproceed. Although alkaline catalysts are preferred, acidic or neutralcatalytic materials may be used if desired. Con-. densation ensuesreadily and the resulting nitroalcohol .Qmay then be isolated byprecipitation with water or other suitable means. In case'an odor, andwhich can be distilled under normal alkaline catalyst is employed theIntro-alcohol is often obtained as its sodium salt (sodium nitrolate).In such instances, the free compound (alcohol) may be secued by directacidification. Although any one of numerous acids (e. g., hydrochloricor'sulphuric) maybe used, acetic acid is preferred for this purpose. Byus'i-ngthe proper proportions *ofreactants, and adding the'aldehyde tothe nitro compound, the intermediate product resulting will consistprincipally of nitro-alcohols with negligible'quantities ofnitro-glycols. The nitro-alcohols thus obtained are afterwardssubjectedto acid hydrolysis. By the term acidhydroly'sis is meantsubjecting the nitro-alcohol to the actionof a concentrated aqueoussolution of an acid, as for' example, hydrochloric acid. This latterstep (acid hydrolysis) may be carried out;

at room temperature or at elevated temperatures, W

and/or pressures, whereupon is obtained mandelic acid, or a derivativeor homologue thereof, along with hydroxylamine hydrochloride which ismuallypresent in the cooled hydrolysis mixture 7 as lustrous whitecrystalsof hlghpurity. When I benzaldehyde and nitromethane are thestarting materials, the reactions may be represented as follows: y 5

dl-Mandelic acid Hydrorylamine hydrochloride The hydrolysis may,depending on the nature of the intermediate nitro-alcohol, require tem-'peratures in the range of -125 C. In such cases the intro-alcohol ismixed with the acid hydrolyzing agent in a suitable reaction vessel,

said vessel being constructed for operation under elevated pressuressuch; as would be developed by the'reaction under the conditionsemployed. The" reactio'n'vessel, which may consist, for example, of apressure autoclave of acid resistant material or of enamelor glass-linedconstruction, may 1 or may not be equipped with a stirringdevice', asdesired. After the reaction period the hydrolysis product is removedfrom the autoclave and the desired materials separated therefrom/In casehydrochloric-acid is employed'asthe hydrolysis" agent, somealpha-chlorocarboxylic acid mayIresult (in the case of benzaldehyde andnitromethane some phenyl alpha-chloroacetic acid may be found in theproduct alongwith mandelic acid) along withthe correspondingalpha-hydroxycarboxylic acid. However, the alpha-chloroacids are quiteeasily converted (in subsequent operations) in presence of water or verydilute alkali, to the corresponding hydroxy-acids. 7 t

The main hydrolysis mixture, 'fromf'which' white crystals of'hydroxylamine hydrochloride separate on-coolin'g, may be fractionatedin any one of several ways. Oneprocedure is as follows: Most ofvegetable charcoal, fullers earth,

hydroxy acids.

2,146,080 the hydroxylamine hydrochloride may preferably be separated,in a high state of purity, by raking or other mechanical means. Theremainder of the hydrolysis product may be diluted with water,neutralized with dilute caustic soda to dissolve carboxylic acids, andthen warmed gently to convert any chloro-acids which might be present toThe solution is then filtered to remove any small amount of oilyunhydrolyzed nitroalcohol. The removal of a possible yellowishcolor'from the resulting solution may then be accomplished in either oftwo ways, as desired. A

small amount of decolorizing carbon, animal or or other decolorizingmaterial may then be added to the solutionof sodium carboxylate, themixture heated for a short time, filtered, and then acidified toliberate the carboxylic acid. This procedure is to be preferred in casethe free hydroxy-acid is of In case, however, the

limited solubility in water. hydroxy-acid is easily soluble in warm orhot water, the acidification to release the free carboxylic acid may bemade prior to the decoloriza- .tion step. The above clarificationtreatment gives a solution possessing very little or no color, fromwhich, by cooling and/or partial evaporation of solvent, crystals of thedesired hydroxycarboxylic acid of high purity are obtained. In case thefinal acid should not possess the proper solubility in water to enableits separation and purification by the above treatment,othersolvent'ssuch as alcohol, or ether, etc., may be substituted whollyor in part, for water, as the solvent medium. It is intended that theabove procedure maybe modified whenever necessary, depending upon thecharacteristics of the individual materials concerned, without deviating'f rom the limits of this invention. As an illustration: in thepreparation of substances such as "drous methanol were added, inportions, 23 parts I by weight of sodium metal. .This was followedlactic acid, from acetaldehyde and nitromethane,

according to the present invention, said acid may be too soluble invwater to be separated by the above means. In such cases, other solventsor even distillation may be resorted to in order to isolate the desiredproducts.

The following typical examples will serve toillustrate my invention.

.Ex ampl e 1.To 350 parts by weight of anhyby. the addition of 61 partsby weight of nitromethane, the temperature being maintained at recoveredby decantation. The yield was 133 parts by weight or 80 per cent of thetheoretical.

This reddish oil appeared to be quite stable on standing forconsiderable periods, especially i1: kept in a cool place. It possesseda specific gravity of about 1.21.

Example 2.A mixture of 5 parts by weight of phenylmitroethanol asobtained from Example 1, and 11 parts by weight of fuming hydrochloricacid (saturated at 0 C. to +5 C.),was sealed in a thick-walled Pyrextube. This reaction tube was then inserted into an oven and mainmelt at148 C. (theoretical 151 C.). mainder of the hydrolysis productwasthinned tained at 110 C. for 6 hours. On cooling to room temperature thetube was found to contain a heavy brownish gummy mass, above which was aclear, slightly yellow, aqueous layer in which were lustrous whitecrystals of hydroxylamine hydrochloride. This latter material wasseparated by mechanical means and was found to The '.'e-

with water and the carboxylic acids dissolved bythe addition of causticsoda. The alkaline solution was then warmed gently (in order tohydrolyze any alpha-chloro acids which may have been present) andfiltered free of a small amount of brownish oil, presumably unhydrolyzednitroalcohol. The clear filtrate was then heated for a short time with asmall amount of decolorizing carbon, in order to remove a slight yellowcolor possessed by the solution, and afterwards filtered free of carbonparticles. The filtrate was acidifled with hydrochloric acid, whilestill warm, and then allowed to cool. In this manner a crop of whitecrystals of dl-mandelic acid of melting point 118 C. (theoretical 118.1C.) was obtained. The. aqueous mother liquor was then extracted with asmall portion of diethyl ether. By slow evaporation of the latterseveral additional small crops of mandelic acid (melting point 118 C.)were obtained. The total yield of purified dlmandelic acid amounted to3.2 parts by weight (71 per cent yield on phenyl-nitroethanol; 57 percent yieldon'benzaldehyde). The mandelic acid thus obtained was shown bya color test with sodium nitroprusside to be free of hydroxylamine.

It will be seen from the foregoing that my invention contemplatescondensation of nitromethane'with an aldehyde to give a nitro-alcohol.The aldehyde employed may be derived from an aliphatic, aromatic, orcycloparaflln hydrocarbon. Another step in my invention comprises thehydrolysis of such a nitro-alcohol, preferably in an acid medium, to analpha hydroxycarboxylic acid and hydroxylamine, the latter beingrecovered as a salt of the acid employed in the hydrolytic operation, Asindicated previously, this latter step involves a rupture of thenitro-alcohol'to give two products (hydroxycarboxylic acid and salt oi.hydroxylamine) both of which may find applications in many various ways.

What I claim is:v

1. The process which comprises condensing an aldehyde with nitromethaneand subjecting the condensation product to acid hydrolysis.

2. The process which comprises condensing an aldehyde with nitromethanewhereby a nitro-alcohol is produced, and subjecting said nitroalcohol toacid hydrolysis whereby an alpha hydroxycarboxylic acid and ahydroxylamine salt are obtained.

3. The proces which comprises condensing an aldehyde with nitromethanewhereby a nitroalcohol is produced, subjecting said nitro-alcoholto-acid hydrolysis whereby an alpha hydroxycarboxylic acid and ahydroxylamine salt are obtained, and separating said hydroxylamine saltfrom said alpha hydroxycarboxylic acid.

4. The process, according to claim 3, in which the aldehyde isbenzaldehyde.

5. The process according to claim 3 in which the aldehyde is an aromaticaldehyde.

. 6. The process according to claim 3, in which acid hydrolysis iseflected with hydrochloric acid.

CARIETON ELLIB.

